Inhibition of protein synthesis is a validated target for the identification of compounds having antibacterial activity. This reflects the reality that protein synthesis is an essential process in prokaryotes, and such organisms employ protein synthesizing systems that differ in many respects from those in eukaryotes. By focusing on a single molecular locus unique to bacteria, Pinnacle has identified a process in bacterial protein synthesis that can be inhibited uniquely and has developed a high throughput assay to permit the identification of natural products that target this prokaryotic locus. Limited screening of natural products extracts has identified several species capable of targeting E. coli protein synthesis. The specific aims of the present proposal include more extensive screening to identify potent and selective inhibitors of the prokaryotic enzyme and characterization of the active agents. Relevance: Many bacterial pathogens that could be treated easily in the clinic have developed resistance to commonly used antibacterial agents. These resistant organisms represent a growing threat to public health and there is a corresponding need to develop new classes of agents for antibacterial therapy. The long term goal of this project is the identification of such agents. [unreadable] [unreadable] [unreadable]